Mouse Genome Informatics
tg
    Tg(Prnp-SNCA*A53T)25Mkle/0
involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• within 14-21 days of onset of motor problems and disease onset, mutants rapidly progress to death most likely due to inability to feed and drink

nervous system
• average age of onset of clinical abnormalities is 15.7 +/- 4.2 months, however 50% of mutants fail to develop disease at 24 months of age
• neuropathological abnormalities develop before motor dysfunction is visible
• astroglial reaction is seen in the midbrain, deep cerebellar nuclei, brainstem and spinal cord, indicating neurodegeneration, but not in the cortex, hippocampus, thalamus, and caudate/putamen
• mutants exhibit accumulation of ubiquitin and phosphorylated Nefh (NF-H) in perikarya and neurites
• affected neurons contain fibrillar inclusions
• abnormal neuronal accumulations are not seen in mutants younger than 4 months of age
• mutants exhibit accumulation of alpha-synuclein in neuronal cell bodies and neurites of the midbrain, cerebellum, brainstem and spinal cord
• spinal cord exhibits astrocytic response and ubiquitin and alpha- synuclein accumulation in ventral horn motor neurons
• mutants develop adult-onset neurodegenerative disease
• astroglial reaction is seen in the midbrain, deep cerebellar nuclei, brainstem and spinal cord, indicating neurodegeneration

behavior/neurological
• mutants develop motor signs characterized by sustained posturing, reduced amplitude, and abundance of spontaneous activity with age
• mutants eventually develop progressive loss of righting reflex
• mutants eventually develop paralysis

muscle

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 1, Autosomal Dominant; PARK1 168601 J:77344